Safety and Preliminary Efficacy Trial of BNT142 in Patients With CLDN6 Positive Solid Tumors
Study Details
Study Description
Brief Summary
This trial is an open-label, multicenter, Phase I/IIa, dose escalation, safety, and pharmacokinetics (PK) trial of BNT142 followed by expansion cohorts in patients with Claudin 6 (CLDN6)-positive advanced tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BNT142
|
Biological: BNT142
Intravenous bolus/infusion
|
Outcome Measures
Primary Outcome Measures
- Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to trial treatment [From first dose to 60 days after the last dose of BNT142]
- Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs [From first dose to 60 days after the last dose of BNT142]
- Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1, i.e., 21 days after the first dose) during the dose escalation [assessed during the first cycle (21 days) in each cohort]
- Part 2: Objective response rate (ORR) [at least 48 months subsequent to first dose, are lost to follow-up, or have died]
ORR is defined as the proportion of patients in whom a complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and per Gynecological Cancer Intergroup (GCIG) criteria incorporating RECIST 1.1 and cancer antigen (CA) 125 for the ovarian cancer population is the best overall response.
Secondary Outcome Measures
- Part 1: PK parameter: Area under the concentration-time curve in the dosing interval (AUC) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Clearance (CL) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Volume of distribution (Vd) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Maximum observed concentration (Cmax) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Time to maximum observed concentration (Tmax) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Concentration prior to next dose (Ctrough) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Minimum observed concentration (Cmin) [pre-dose until 60 days after last dose]
- Part 1: PK parameter: Elimination half-life (t½) [pre-dose until 60 days after last dose]
- Disease control rate (DCR) [at least 48 months subsequent to first dose, are lost to follow-up, or have died]
DCR is defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1 [and per GCIG criteria for ovarian cancer patients], SD assessed at least 6 weeks after first dose) as best overall response.
- Duration of response (DOR) [at least 48 months subsequent to first dose, are lost to follow-up, or have died]
DOR is defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST 1.1) or death from any cause, whichever occurs first.
- Anti-drug antibodies (ADAs) response [pre-dose until 60 days after last dose]
ADAs response assessed with BNT142-encoded protein anti-RiboMab02.1, and anti-polyethylene glycol (PEG) lipid antibodies.
- Part 1: ORR [at least 48 months subsequent to first dose, are lost to follow-up, or have died]
ORR (Part 1 only; this is a primary endpoint for Part 2) is defined as the proportion of patients in whom a CR or PR, per RECIST 1.1, is the best overall response.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
For Part 1 and 2:
-
Histological or cytological documentation of a solid tumor that is metastatic or unresectable via a pathology report.
-
CLDN6-positive tumor sample as assessed by central testing using a validated immunohistochemistry (IHC) assay in formalin-fixed paraffin-embedded (FFPE) neoplastic tissues. FFPE tissue can be derived from fresh biopsies and archival samples. If archival tissue samples from several points of time are available, the most recent one is preferred.
-
Measurable disease per RECIST 1.1 (measurable per RECIST 1.1 or evaluable per GCIG criteria for ovarian tumors).
For Part 1 (Dose escalation):
- Patients with advanced/metastatic ovarian, non-squamous non-small cell lung cancer (NSCLC), endometrial, or testicular cancer, for whom there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy, or patients with not otherwise specified (NOS) tumors not included in the eligible tumor types, including rare tumors and cancers of unknown primary, upon approval by the medical monitor. Patients must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the Food and Drug Administration (FDA), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO) or local guidelines used at the site), and failed at least first line standard of care (SOC) therapy prior to enrollment.
Key Exclusion Criteria:
-
Radiotherapy, chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of trial treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment.
-
Concurrent systemic (oral or intravenous [IV]) steroid therapy >10 mg prednisone daily or its equivalent for an underlying condition apart from physiologic corticosteroid replacement therapy.
-
Major surgery within 4 weeks before the first dose of BNT142.
-
Ongoing or active infection requiring IV treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of BNT142.
-
Prior treatment with a CLDN6 targeting monoclonal antibody.
-
Side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5 Grade ≤1, with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must have recovered to Grade ≤2. Alopecia of any grade is allowed.
-
Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain metastases may be eligible if they:
-
Had radiotherapy, surgery or stereotactic surgery for the brain metastases;
-
Have no neurological symptoms (excluding Grade ≤2 neuropathy);
-
Have stable brain metastasis on the computer tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent form (ICF); and
-
Are not undergoing acute corticosteroid therapy or steroid taper.
-
Notes: Patients with central nervous system (CNS) symptoms should undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases are allowed, unless imminent fracture with cord compression is anticipated.
-
Pregnant or breastfeeding or planning to get pregnant within 6 months of the last dose of BNT142.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 2 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 3 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 4 | South Texas Accelerated Research Therapeutics (START) - San Antonio | San Antonio | Texas | United States | 78229 |
| 5 | NEXT Virginia | Fairfax | Virginia | United States | 22031 |
| 6 | National University Cancer Institute - National University Hospital | Singapore | Singapore | 119074 | |
| 7 | Hospital Universitario Vall D'Hebron | Barcelona | Spain | 08035 | |
| 8 | MD Anderson Cancer Center | Madrid | Spain | 28033 | |
| 9 | START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz | Madrid | Spain | 28040 | |
| 10 | START Madrid CIOCC Hospital Universitario HM Sanchinarro | Madrid | Spain | 28050 |
Sponsors and Collaborators
- BioNTech SE
Investigators
- Study Director: BioNTech Responsible Person, BioNTech SE
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BNT142-01